SETD3 protein is the actin-specific histidine N-methyltransferase.

ABSTRACT: Protein histidine methylation is a rare post-translational modification of unknown biochemical importance. In vertebrates, only a few methylhistidine-containing proteins have been reported, including ?-actin as an essential example. The evolutionary conserved methylation of ?-actin H73 is catalyzed by an as yet unknown histidine N-methyltransferase. We report here that the protein SETD3 is the actin-specific histidine N-methyltransferase. In vitro, recombinant rat and human SETD3 methylated ?-actin at H73. Knocking-out SETD3 in both human HAP1 cells and in Drosophila melanogaster resulted in the absence of methylation at ?-actin H73 in vivo, whereas ?-actin from wildtype cells or flies was > 90% methylated. As a consequence, we show that Setd3-deficient HAP1 cells have less cellular F-actin and an increased glycolytic phenotype. In conclusion, by identifying SETD3 as the actin-specific histidine N-methyltransferase, our work pioneers new research into the possible role of this modification in health and disease and questions the substrate specificity of SET-domain-containing enzymes.

SUBMITTER: Kwiatkowski S 

PROVIDER: S-EPMC6289574 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature